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Biomedical subjects

R C Bennett

Publications and source records attributed to R C Bennett.

At least 19 recordsLinked to original sources

Rearrangement of chromosome 1p in breast cancer correlates with poor prognostic features.

In a cytogenetic study of breast cancer biopsies, clonal abnormalities of chromosome 1p were identified in 56% (14) of 25 informative patients. Translocations predominated, involving 1p22 (n = 1), 1p35 (n = 1) or 1p36 (n = 10) breakpoints. Chromosome 1p abnormalities were associated with estrogen receptor (ER) negativity (P = 0.03, 2-tailed Fisher Exact Probability test), high histological grade (P = 0.02, 2-tailed Mann-Whitney U-test) and an unfavourable Melbourne Prognostic Score (NEPA P = 0.02, SEPA P = 0.04, 2-tailed Mann-Whitney U-tests). These findings are consistent with the possibility that a gene located on chromosome 1p is implicated in tumour progression.

Biomarkers, Tumor

Breast cancer in the elderly: treatment of operable disease.

Between 1976 and 1985 122 elderly patients aged 70 years and over, were treated for 'operable' invasive breast cancer (UICC stage I-IIB). A tendency towards less aggressive investigation and treatment was noted in the elderly. Of 117 patients undergoing surgery, 79 (68%) had 'full' conventional treatment, either mastectomy with axillary clearance, sampling or radiotherapy, or local excision with radiotherapy. In 38 patients (32%) management of the breast or axilla was considered to have been less complete than the usual practice for younger patients ('limited' treatment group), either local excision without radiotherapy or simple mastectomy alone. The 'limited' treatment group were significantly older than the 'full' treatment group but were comparable for tumour size, clinical nodal status and oestrogen and progesterone receptor levels. Although there was no survival difference between the groups, those in the 'limited' treatment group were more likely to develop locoregional recurrence (chi 1(2) = 9.2, P = 0.002, log rank test). In practice, management of the elderly often appears to be influenced by chronological age rather than clinical or biological factors. It is suggested that elderly patients sufficiently fit to undergo surgery should be treated along the lines applicable to younger patients.

Age Factors

Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites.

Parathyroid hormone-related protein (PTHrP) has recently been identified in 60% of a series of primary breast cancers. The detection of a bone-resorbing factor in tumors with a propensity to metastasize to bone prompted study of PTHrP in breast cancer metastasis. PTHrP was localized by immunohistology in 12 of 13 (92%) breast cancer metastases in bone and in 3 of 18 (17%) metastases in non-bone sites. The statistical difference was highly significant (P less than 0.0001). Production of PTHrP as a bone-resorbing agent may contribute to the ability of breast cancers to grow as bone metastases.

Bone Neoplasms

Cytogenetic features of twenty-six primary breast cancers.

Tumor preparations from 26 primary breast cancers were studied cytogenetically with G-banding, using a direct technique, synchronized short-term culture, or both. Two tumors had normal karyotypes, and 24 (92%) had chromosomal abnormalities. Nineteen tumors had chromosome 1 rearrangements, with 10 cases (40%) displaying distal short arm translocations (1p36). Other frequent breakpoints occurred at 3p21, 6q22-27, 11q21-25, 16q22-24, 17p, and 19q13. To seek primary rather than secondary cytogenetic changes, attention was directed toward tumors with diploid-range karyotypes (32-57 chromosomes per cell). Of four such tumors, three exhibited nonrandom involvement of chromosome 16q22. This, together with previously reported data, suggests that deletion or rearrangement of chromosome 16q21-24 may be a primary or specific event in a subset of breast cancers.

Adenocarcinoma, Mucinous

The prognostic value of immunoperoxidase staining with monoclonal antibodies NCRC-11 and 3E1.2 in breast cancer.

The variation in survival of women with clinically similar breast cancers may lead to difficulty in clinical management so it is important to recognise factors which indicate the prognosis. Immunoperoxidase staining patterns of primary breast tumours using monoclonal antibody NCRC-11 have been shown to relate to overall survival (Ellis et al., 1985) but the results have not been reproducible in other centres. In this study paraffin sections of 483 primary breast cancers were stained with NCRC-11 and 3E1.2 using an immunoperoxidase system. The tumour staining patterns were compared with overall survival using life tables and tested for relative prognostic significance by Cox's multivariate analysis. NCRC-11 related to survival in all 483 cases (chi 2 5.8, P = 0.02) but both antibodies achieved maximum prognostic significance in lymph node negative patients (chi 2 9.4, P less than 0.002 and chi 2 10.7, P less than 0.001) in whom no other factor was more significant. Immunoperoxidase staining patterns produced by monoclonal antibodies NCRC-11 and 3E1.2 are important prognostic factors in breast cancer.

Antibodies, Monoclonal

Breast cancer in the elderly: pattern of disease.

The elderly (aged 70 years or more) constituted 201 (37%) of 548 first-time admissions to a single institution for breast cancer between 1976 and 1985. The pattern of disease was studied and contrasted with that seen in younger patients (less than 70 years old). Currently, 5000 new breast cancers are diagnosed in Australia each year. It is projected that the proportion of new breast cancer patients who are elderly will rise from 37 to 60% by the year 2031. In general, the disease was similar to that seen in younger patients. Minor histological differences occurred and there were tendencies towards late presentation and clinically less aggressive disease. Tumour size, the presence of metastases and UICC staging were useful predictors of outcome but nodal status and hormone receptor levels did not discriminate. An unexpected finding was the relative longevity of elderly patients with breast cancer. The stage-specific 5-year survival rates (UICC stages: I--73%; II--65%; III--42%; IV--10%;) did not differ significantly from those seen in younger patients.

Aged

Oestrogen receptor assay of breast cancer by immunocytochemistry of fine needle aspirates.

Sixty-five patients with operable breast cancer were studied to assess the reliability of immunocytochemical analysis of oestrogen receptor (ER-ICA) in specimens obtained by percutaneous fine needle aspiration. Results obtained with the commercially available ER-ICA kit were compared with those obtained by the routine biochemical radioligand assay of oestrogen receptor (ER) on excised tumour specimens. Fifty-two of 65 percutaneous aspirates were evaluable. Of these, thirty-five (67%) were ER positive by the radioligand method. ER-ICA was found to be a reliable method for oestrogen receptor assay, with a high concordance (90.4%) between it and the radioligand essay. The ER-ICA assay had a sensitivity of 89%, specificity of 94%, positive predictive value of 97% and negative predictive value of 80%. ER-ICA assay performed on material obtained by fine-needle aspiration is a reliable method of ER assay. It can replace formal biopsy for patients with inoperable primary tumours or accessible metastases.

Adenocarcinoma, Mucinous

Trends in the content and use of oral contraceptives in the United States, 1964-88.

Drug marketing and physician survey data were used to examine trends in the use and hormonal content of oral contraceptives in the United States between 1964 and 1988. Retail prescriptions for oral contraceptives peaked at approximately 68 million in 1973 and have remained between 50 million and 60 million since 1981. Despite this relative consistency in the number of prescriptions, physician "mentions" of oral contraceptives have increased by approximately 75 percent. This increase may reflect closer monitoring of women on oral contraceptives. Use of multiphasic formulations has steadily risen, accounting for 37 percent of the oral contraceptive prescriptions in 1988. Mean estrogen and progestin doses in all types of formulations have steadily declined. A change in the type of estrogen and progestin used in preparations has coincided with this decline in dose. The association between age and use of high-dose formulations seen in the past was no longer evident in 1988. The data demonstrate that oral contraceptive formulations in wide use today differ in hormone content from those of the past, when most of the major studies addressing the risks associated with oral contraceptive use were completed. There is therefore a need to determine the risks and long-term effects associated with these newer formulations.

Adolescent

Comparison of EGFR, c-erbB-2 product and ras p21 immunohistochemistry as prognostic markers in primary breast cancer.

In a prospective study of 75 breast carcinomas, monoclonal antibodies EGFR1, Anti-serum 21N (As21N) and RAP-5 were used to assess immunohistochemically expression of Epidermal Growth Factor Receptor (EGFR), c-erbB-2 oncoprotein and ras protein p21. A careful comparison was made of their relative prognostic significance. Positive staining was seen with EGFR1 in 12/71 cancers (17%) and with As21N in 16/75 cancers (21%). Positive staining with RAP-5 occurred in all cancers and benign breast tissue, but varied in intensity. EGFR expression correlated with the number of involved lymph nodes, histological grade, estrogen and progesterone receptor (ER, PR) levels and the Melbourne Prognostic Index. C-erbB-2 and ras expression both correlated with ER levels and EGFR, but not with the Prognostic Index. Based on an immunohistochemical technique, EGFR expression emerges as the parameter with strongest prognostic associations.

Biomarkers, Tumor

Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer.

Parathyroid hormone-related protein (PTHrP) is known to be a causative factor in humoral hypercalcemia of malignancy. A polyclonal rabbit antiserum directed against the amino-terminal region of the protein and immunoperoxidase methods have been used to locate the presence of PTHrP in a series of 102 consecutive invasive breast tumors removed surgically from normocalcemic women. Positive PTHrP staining was detected in 60% of the tumors but not in the accompanying normal breast tissue. Positive staining was related to the progesterone receptor status of the tumor (P = 0.039) and to the prognostic index of the patient (P = 0.046) and not to estrogen receptor status, patient age, tumor size, histological grade, or nodal status.

Age Factors

Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism.

To assess possible differences in the incidence of venous thrombosis and pulmonary embolism associated with oral contraceptives of varying hormonal potencies, the authors conducted a retrospective cohort study in the 15-44 year old Michigan Medicaid population. Cohorts were defined by the progestin- and oestrogen-potencies of oral contraceptives in use at the time of follow-up as classified by an oral contraceptive potency scheme. Using the low-oestrogen-/low-progestin-potency formulations for reference (rate ratio = 1), adjusted rate ratios of 0.8 (95% CI: 0.5 to 1.3, P = 0.41) and 0.6 (95% CI 0.4 to 1.2, P = 0.13) were observed for intermediate-progestin-potency and high-progestin-potency formulations, respectively. Adjusted rate ratios of 1.4 (95% CI: 0.8 to 2.3, P = 0.21) and 2.6 (95% CI: 1.2 to 5.5, P = 0.01) were observed for intermediate- and high-oestrogen-potency formulations. These data suggest a dose-response relationship between oral contraceptive oestrogen potency and venous thromboembolism, whereas no such evidence for a dose-response relationship between oral contraceptive progestin potency and venous thrombo-embolism was found.

Adolescent

Incidence and toxicological aspects of cannabis and ethanol detected in 1394 fatally injured drivers and pedestrians in Ontario (1982-1984).

A comprehensive epidemiological study of the involvement of cannabis and ethanol in motor vehicle fatalities in the Province of Ontario, Canada, is described. The study is based on toxicological analyses of blood and, when available, urine specimens. Ethanol was determined by headspace gas chromatography (GC). For cannabis, the methods employed were radioimmunoassays (RIAs) for screening and gas chromatography/mass spectrometry (GC/MS) for the determination of delta-9-tetrahydrocannabinol (THC) in blood. The study sample consisted of 1169 drivers and 225 pedestrians. THC was detected in the blood of 127 driver victims (10.9%) in concentrations ranging from 0.2 to 37 ng/mL, with a mean of 3.1 +/- 5.0 ng/mL. Ethanol was found in 667 driver victims (57.1%), in concentrations ranging from 9 to 441 mg/100 mL, with a mean of 165.8 +/- 79.5 mg/100 mL. For pedestrians, the incidence of THC and ethanol in the blood was 7.6 and 53.3%, respectively. The incidence of THC in the driver victims in this study constitutes an approximately threefold increase over the results of an Ontario study completed in 1979. At least a part of the increase may be attributed to interstudy differences in analytical methodology for cannabinoids.

Accidents, Traffic

Controlled clinical trial of adjuvant immunotherapy with BCG and neuraminidase-treated autologous tumour cells in large bowel cancer.

A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.

Adenocarcinoma

Estrogen receptors in bilateral breast cancer.

Estrogen receptor status, tumor histology, and the interval between the development of tumors were assessed in 99 patients with bilateral breast cancer. Tumors were first grouped into those simultaneously detected in both breasts or within 12 months of each other (synchronous bilateral breast cancer, of which there were 64) and second, those detected within more than 12 months of each other (asynchronous bilateral breast cancer, of which there were 35). Nineteen percent of all tumors were lobular carcinomas. Overall, the rate of receptor discordance between the two tumors was not significantly different from that previously reported between biopsies of primary tumor and metastases in patients with unilateral breast cancer. Synchronous receptor-positive tumors occurred significantly more frequently than expected, suggesting that the development of the two tumors was influenced by a common mechanism. In patients with asynchronous bilateral breast cancer there was a significantly longer interval between tumors if both were receptor-positive compared with concordant receptor-negative tumors and tumors with discordant receptor status. There was a significant discordance in the receptor status of asynchronous tumors when the histology also differed, indicating that the tumors in this group were likely to be separate primary tumors.

Breast Neoplasms

Melbourne trial of adjuvant immunotherapy in operable large bowel cancer.

A controlled randomized clinical trial was undertaken to assess the ability of combined non-specific and specific immunotherapy to alter the disease-free interval and overall survival of patients with Stage B or C large bowel cancer. The immunotherapy consisted of a 2 year programme of vaccinations with BCG and neuraminidase-treated autologous tumour cells. Three hundred and one patients entered the trial. At 5 years of follow-up there is no evidence that this form of immunotherapy can alter either the disease-free interval or survival in this group of patients.

Antigens, Neoplasm

The role of surgery in advanced carcinoma of the breast.

The role of surgery in the management of advanced carcinoma of the breast is controversial. Locally advanced carcinoma may present as a primary tumour or as recurrent disease. Treatment should be the result of a multi-disciplinary approach and may involve one or more different modalities. Minor surgery is usually meddlesome and often followed by local recurrence which is hard to control. Major resection does have a place, often in association with other modalities of treatment, and its use in carefully selected patients is described in this paper.

Breast Neoplasms